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Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways

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Abstract

Intracellular calcium oscillation and its downstream signaling in osteoclasts is believed to play critical roles in regulating bone resorption. Our previous study demonstrated that fluid shear stress (FSS) induced more calcium responsive peaks in the late differentiated osteoclasts than the early ones. In this paper, the signaling pathways of FSS-induced calcium response for the osteoclasts in different differentiation stages were studied. RAW264.7 macrophage cells were induced to differentiate into osteoclasts with the conditioned medium from MC3T3-E1 osteoblasts. Furthermore pharmacological agents were added to block the specific signaling pathways. Finally the cells were exposed to FSS at different levels (1 or 10 dyne/cm2) after being induced for 4 or 8 days. The results showed that the mechanosensitive, cation-selective channels, phospholipase C (PLC) and endoplasmic reticulum constituted the major signaling pathway for mechanical stimulation-induced calcium response in osteoclasts. Extracellular calcium or ATP involved with calcium oscillation in a FSS magnitude-dependent manner. This pathway study may help to give insight into the molecular mechanism of mechanical stimulation-regulated bone remodeling.

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Acknowledgment

This work was supported by the National Natural Science Foundation of China [11372043 (BH) and 31070829 (DZ)], National Key Basic Research Foundation of China grant [2011CB710904 (ML)] and the Fundamental Research Funds for the Central Universities [GZ2013015101 (BH)].

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No conflict of interested is assigned to the manuscript.

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Authors and Affiliations

  1. Department of Mechanics, School of Aerospace Engineering, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Beijing, 100081, People’s Republic of China

    Ping Li, Chenglin Liu & Bo Huo

  2. Department of Stomatology, Faculty of Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

    Ping Li & Ding Zhang

  3. Key Laboratory of Microgravity and Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Ping Li, Man Hu, Mian Long & Bo Huo

  4. Department of Maxillofacial & E.N.T. Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China

    Ping Li

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  1. Ping Li
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Correspondence to Ding Zhang or Bo Huo.

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Associate Editor Scott I. Simon oversaw the review of this article.

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Li, P., Liu, C., Hu, M. et al. Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways. Ann Biomed Eng 42, 1250–1260 (2014). https://doi.org/10.1007/s10439-014-0984-x

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  • DOI: https://doi.org/10.1007/s10439-014-0984-x

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